L0301P85 - Natural Barriers, Innate Defence, and the Host-Parasite Relationship
Disease *deviation/interruption of normal structure/function of any part of the human body that is manifested by a characteristic set of symptoms or signs *microorganisms that cause disease include: **bacteria, fungi, yeasts, viruses, protozoa, helminths (parasites) Immunity *system enables us to resist infections *composed of two major subdivisions **innate (antigen non-specific) system ***first and second line of defence **adaptive (antigen specific) system *operate together resulting in coordinated defence system Antigen *any molecule that elicits an immune response (antibody generator) *e.g. parts of bacteria, virus, pollen, dust Antibody *a protein made by the bodies immune system that reacts with specific antigens Characteristics of Innate Immunity *responses: **are broad-spectrum (non-specific) **occur immediately or within several hours **are phylogenetically ancient *no memory or lasting protective immunity *limited repertoire of recognition molecules Body’s Natural Defence Barriers *anatomical *mechanical *antimicrobial/chemical factors *cellular components *normal flora - our microbiota Anatomical Barriers Skin *physical barrier/primary innate defence against invasion *arid, salty, acidic environment Mucous Membranes *line body cavities open to the exterior *respiratory tract, GIT, genitourinary tract Mechanical Defences *mucus *ciliary action in respiratory tract *coughing and sneezing *vomiting and diarrhoea *physical flushing when urinating *blinking *peristalsis in GI tact Antimicrobial/Chemical Factors Acids and Enzymes *fatty acids, lactic acid **limits types of bacteria that can live on those surfaces **e.g. on skin *gastric acid in the stomach **too acidic for most bacteria to survive in *pepsin **digestive enzyme which hydrolyses proteins in the stomach *lysozyme **hydrolytic enzyme able to cleave the peptidoglycan of bacterial cell walls **present in mucous secretions, saliva, serum, tears and sweat Antimicrobial Substances *directly destroy micro-organism *short peptides - cryptidins and defensins **bore holes in bacterial cell membranes Cytokines and Chemokines *small protein signalling compounds *secreted by many epithelial cells *e.g. **IL-8 (CXCL8) - pro-inflammatory **interferons Complement *group of serum proteins that circulate in the blood in an inactive (proenzyme) state *can be activated by a variety of mechanisms *three main pathways **classical, lectin and alternative ***lectin and alternative pathways are part of innate immune system *two main effects: **membrane attack complexes (proteins) embed in cell membranes causing lysis **attach to surfaces of bacteria/viruses and target them for destruction by phagocytes (opsonisation) Cellular Components - White Blood Cells Phagocytic Cells *monocytes *dendritic cells *neutrophils **most abundant type of WBC **ingest or trap microorganism and particles and destroys them **pus = large numbers of neutrophils, tissue cells and dead pathogens *macrophages **engulf pathogens and dead cell remains **most circulate in the blood, lymph and extracellular fluid Granulocytes *cells that release inflammatory mediators *include: basophils, mast cells, eosinophils Natural Killer Cells *attack the body’s own cells that have become infected by viruses *attack potential cancer cells, often before they form tumours *bind to MHC markers of cells, if they are detected as infected, they kill them by secreting perforin - makes holes in the cell membrane of the target cell. Inflammation *non-specific response to injury, pathogens, irritants that occur in a vascularised tissue *signs of acute inflammation: **redness - vasodilation **heat - vasodilation, endogenous pyrogens (heat inducing molecules) **swelling - increased vascular permeability and migration of leukocytes **pain - stimulation of neuronal pathways **loss of function - depending on severity *provides early protection by restricting tissue damage to the site of infection *occurs when pro-inflammatory cytokines (TNF, IL-1) signal endothelial cells to be: **leaky to fluid - influx of plasma; containing antibodies, complement components, etc. **sticky for white blood cells ***allows them to slow down and leave the blood flow into the tissue (most important feature of inflammation) *may also be triggered by activation of the complement system or coagulation system Fever (Pyrexia) *often accompanies inflammation *important signal to the body that there is something wrong *natural reaction to a number of illnesses *many infections are called fevers *signs: **body temperature above 37°C **associated with sweating, hyperventilation and vasodilatation in the skin *allows a more rapid recovery from infections or critical illness **important immunological reactions are sped up by temperature **the growth of some pathogens with strict temperature preferences is hindered Summary Normal Flora *in a healthy human, internal tissues are usually free of microorganisms **e.g. brain, blood, cerebrospinal fluid *whereas surfaces that are in constant contact with the environment are colonised by microorganisms **found on skin, upper respiratory tract, gastrointestinal tract, lower urinary tract **none found in lower respiratory tract and upper urinary tract *defined as microorganisms that live on or in the body without causing harm **resident flora - always present **transient flora - not always present *normal flora is exceedingly complex **more than 200-400 different species *each person has their own individual flora *changes continuously throughout life *more micro-organisms are present than human cells **the body which contains about 1013 cells routinely harbours about 1014 bacteria Function *prevent colonisation by potential pathogens out competing the invading microbes Skin Bacteria *take up space and nutrients *produce fatty acids Gut Bacteria *ferment unused energy substrates *provide nutrients to intestinal mucosa *produce bacteriocins and colicins *synthesise and excrete vitamins *train the immune system Vaginal Lactobacilli *help create an acidic environment suppressing growth of other bacteria Host-Parasite Relationship Symbiosis *one species lives in/on the body of another three broad categories Mutualism *two independent organisms living together to their mutual benefit *humans and some of their normal flora species e.g.: **Escherichia coli in the colon ***production of Vitamin K and some B vitamins ***break down waste products ***benefit by assured food supply and sheltered environment Commensalism *association where one benefits while not causing harm to the other *also known as residents, commensals *originally thought that all normal flora were commensals Parasitism *where one organism benefits at the expense of the other *host is usually damaged or disadvantaged while the parasite benefits *ranges from slight harm to death *many parasites are or can become pathogenic and cause disease **include bacteria, viruses, fungi, protozoa or helminth (worms) Normal Flora and Human Relationship *usually commensalistic or mutualistic *are only considered to be in a parasitic relationship when they cause infection Opportunistic Pathogens *clostridium difficile - pseudomembranous enterocolitis *candida albicans - thrush Carry Potential Source of Infection *carrier **active (symptomatic), incubatory (no symptoms yet), convalescent (recovery) *chronic carrier **harbours the pathogen for long periods **multiplication and shed at low levels **absence of symptoms of disease **however host is still capable of transmitting infection